Related Experiment Video
Updated: Aug 6, 2026
07:55
Visualization of DNA Repair Proteins Interaction by Immunofluorescence
Published on: June 26, 2020
RAD51 in Breast Cancer: From Vulnerability to Resistance
Rana Salman Anjum1, Kazuaki Takabe2,3,4,5,6,7,8
1Department of Oral Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.
World Journal of Oncology
|July 23, 2026
Summary
Homologous recombination deficiency (HRD) in breast cancer creates vulnerability to PARP inhibitors. However, RAD51 restoration drives resistance by protecting replication forks, shifting treatment focus to dynamic RAD51 assessment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Homologous recombination deficiency (HRD) is key to breast cancer treatment with PARP inhibitors and platinum chemotherapy.
- RAD51 (Radiation Sensitivity 51) is crucial for DNA repair and replication fork stability, with its deficiency sensitizing BRCA1/2-mutant tumors.
- Restoration of RAD51 function, particularly replication fork protection, emerges as a resistance mechanism against these therapies.
Purpose of the Study:
- To review RAD51 biology, integrating structural, mechanistic, and translational data.
- To propose a dynamic framework for understanding breast cancer evolution under therapeutic pressure.
- To explore strategies for targeting RAD51 in treatment-resistant breast cancer.
Main Methods:
- Literature review integrating structural, mechanistic, and translational insights into RAD51.
- Analysis of RAD51's distinct roles in double-strand break repair versus replication fork protection.
- Conceptual framework development for breast cancer adaptation to therapy.
Main Results:
- Breast cancer evolves from RAD51 deficiency-driven vulnerability to RAD51-dependent adaptive survival.
- RAD51's role in replication fork reversal, stabilization, and restart can confer PARP inhibitor resistance independently of classical HR.
- Therapeutic resistance is linked to RAD51's adaptive functions in replication stress tolerance.
Conclusions:
- Precision oncology for breast cancer must evolve beyond static HRD classification.
- Dynamic assessment of RAD51-dependent replication stress tolerance is critical for refining treatment strategies.
- Targeting RAD51 in PARP inhibitor-refractory and replication stress-high breast cancer presents a promising therapeutic avenue.
Related Concept Videos
02:56Treatment Resistant Cancers
Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
02:53Adaptive Mechanisms in Cancer Cells
Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
02:53Adaptive Mechanisms in Cancer Cells
Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:20The Retinoblastoma Gene
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...